There are seven transmembrane chemokine receptors that act as cofactors for HIV infection. The cofactors enable entry of HIV-1 into CD4+ T cells and macrophages (Premack et al., Nature Medicine 2: 1174-78 (1996); and Zhang et al., Nature 383: 768 (1996)).
The presence of chemokines has an inhibitory effect on HIV-1 attachment to, and infection of, susceptible cells. Additionally, some mutations in chemokine receptors have been shown to result in resistance to HIV-1 infection. For example, a 32-nucleotide deletion within the CCR5 gene has been described in subjects who remained uninfected despite repeated exposures to HIV-1 (Huang et al., Nature Medicine 2: 1240-43 (1996)).
Evidence also exists for the physical association of a ternary complex between chemokine receptors, CD4, and HIV-1 gp120 envelope glycoprotein on cell membranes (Lapham et al., Science 274: 602-05 (1996)). Receptor signaling and cell activation are probably not required for the anti-HIV-1 effect of chemokines since a RANTES analog lacking the first eight amino-terminal amino acids, RANTES (9-68), lacked chemotactic and leukocyte-activating properties, but bound to multiple chemokine receptors and inhibited infection by macrophage-tropic HIV-1 (Arenzana-Seladedos et al., Nature 383: 400 (1996)). Cumulatively, the above described results suggest that the interaction between gp120, CD4, and at least one chemokine receptor is obligatory for HIV-1 infection. Accordingly, reagents that interfere with the binding of gp120 to chemokine receptors and to CD4 are used in the biological and medical arts. However, there presently exists a need for additional reagents that can compete with one or more proteins of the gp120-CD4-chemokine receptor complex to assist in basic biological or viral research, and to assist in medical intervention in the HIV-1 pandemic. It is an object of the present invention to provide such reagents. This and other objects and advantages, including additional inventive features, will be apparent from the description provided herein.